To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Objective:To prepare seven standard strains of 2019 novel coronavirus (2019-nCoV), including wild type (WT) strain, Beta variant, Delta variant, Omicron variants (BA.2, BA.5, BQ.1, XBB.1 branches), which could be used to apply for national standard strains.Methods:According to cytopathic effect (CPE), virus titer, whole-virus-genome-sequencing and detection of mycoplasma, the basic biological characteristics of clonal isolation were determined through plaque purification technology.Results:The CPE was mainly characterized by cell shrinkage and exfoliation in Vero cells after infection with seven 2019-nCoV clonal isolations (WT, Beta, Delta, Omicron, BA.2, BA.5, BQ.1 and XBB.1 branches). The result of mycoplasma detection were negative and titers of the clonal isolation from 2nd to 5th generations were stable at 10 5-10 8 TCID 50/ml; the electron microscope showed that the virions were all round or elliptical, with a diameter between 60 nm and 140 nm. The subtypes of 7 strains were identified by whole-virus-genome-sequencing and phylogenetic analysis, with genomic stability after the fifth successive generations of clonal isolation. Conclusions:The series clonal isolation of 2019-nCoV with typical CPE of coronavirus, clear morphological structure, good viral activity and stable genetic characteristics were prepared, and they could be used to apply for national standard strains.

Objective:To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis.Methods:C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×10 6 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson′s trichrome to assess the extent of renal fibrosis. Results:Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×10 6 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group ( P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group ( P<0.05), but increased again upon addition of SC79. Conclusion:Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

Objective To investigate the levels of plasma bile acids(BA)in patients with primary liver cancer(PLC)or metastatic liver cancer(MLC)and their correlation with clinical indicators,as well as the value of plasma BAs combined with alpha-fetoprotein(AFP)in the diagnosis of PLC.Methods This study was conducted among 75 patients with PLC and 79 patients with MLC who attended Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2020 to September 2021 and had a confirmed diagnosis based on histopathological and imaging findings.Peripheral blood samples were collected from all patients,and serum and plasma were separated.Colorimetry and chromatography were used to measure biochemical parameters;electrochemiluminescence immunoassay was used to measure the levels of tumor markers;liquid chromatography-tandem mass spectrometry was used to measure the content of BA.The t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data;the Spearman's coefficient was used for correlation analysis;the receiver operating characteristic(ROC)curve was used to evaluate clinical diagnostic efficacy.Results The PLC group had significantly lower levels of total cholesterol,triglyceride,low-density lipoprotein cholesterol,and apolipoprotein B than the MLC group(U=1 598,1 255,909,and 889,all P＜0.05).Compared with the MLC group,the PLC group had a significantly higher level of AFP and a significantly lower level of carcinoembryonic antigen(U=1 873 and 926,both P＜0.05).Compared with the MLC group,the PLC group had significantly higher levels of TBA,CA,CDCA,UDCA,TCA,TCDCA,GCA,GCDCA,TUDCA,and GUDCA and a significantly lower level of DCA(all P＜0.05).In the total population,the levels of TBA,CDCA,GCA,GCDCA,GUDCA,TCA,TCDCA,and TUDCA were significantly positively correlated with the level of AFP(all P＜0.05).In the patients with PLC,the levels of GCA,TCA,TCDCA,and TUDCA were significantly positively correlated with the level of AFP(all P＜0.05).Combined measurement of AFP+TCA+GCA+TCDCA had an area under the ROC curve of 0.822(95%confidence interval:0.746-0.898,P＜0.000 1),suggesting that it had the highest diagnostic efficacy.Conclusion There are significant differences in the levels of plasma BA between the patients with PLC and those with MLC,and the differentially expressed BAs are closely associated with liver function impairment and the increase in AFP.BAs combined with AFP has a better clinical value in the diagnosis of PLC.

Objective:To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization.Methods:The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed.Results:(1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm 3 and cone size <2 cm 3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference ( P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm ( RR=3.084, 95% CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm 3 and those with cone size ≥2 cm 3 ( RR=1.700, 95% CI: 0.935-3.092; P=0.077). Conclusion:The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

Carbapenem-resistant enterobacteriaceae(CRE), also known as "super bacteria", has been emerging for several years as a major public-health concern worldwide. The production of carbapenemases is the most crucial resistance mechanism in CRE. The genes encoding carbapenemases can be transmitted by via plasmids, representing a primary cause of nosocomial infections and the widespread proliferation of antibiotic resistance. Carbapenemases, particularly the class A β-lactamases, have long been considered the most crucial resistance mechanism. However, the stealthy dissemination of OXA-48-like carbapenemases presents a more significant threat. OXA-48-like carbapenemases family members have complex composition, with variable hydrolytic activities against β-lactam drugs. They generally demonstrate weaker hydrolytic activity against carbapenems, leading to challenges in detection, which pose significant obstacles in clinical diagnosis, treatment, infection control. Therefore, this review focuses on the OXA-48-like carbapenemases family composition, epidemiology, hydrolytic activity, crystal structure, transmission mode and detection method.

Objective:To observe the proteomic changes in vitreous fluid samples from patients with rhegmatogenous retinal detachment combined with choroidal detachment (RRDCD).Methods:A prospective cross-sectional clinical study. Vitreous fluid samples were collected from 35 patients with RRDCD (RRDCD group) and 40 patients with rhegmatogenous retinal detachment (RRD group) who were diagnosed at Wuhan Aier Eye Hospital between November 2021 and December 2023. Prior to vitrectomy, 0.3-0.5 ml of vitreous fluid was collected from the affected eyes. Differentially expressed proteins were analyzed using Data-Independent Acquisition (DIA). Three of these proteins were randomly selected for validation using enzyme-linked immunosorbent assay (ELISA). Bioinformatics analyses, including gene ontology functional enrichment and kyoto encyclopedia of genes and genomes pathway enrichment, were performed to explore the functions of the differentially expressed proteins.Results:Significant differences were observed between the RRDCD and RRD groups in intraocular pressure ( t=-12.795), the number of retinal tears ( t=4.601), the extent of retinal detachment ( χ2=39.642), axial length ( t=0.840), postoperative proliferative vitreoretinopathy incidence ( χ2=4.730), single-surgery reattachment rate ( χ2=7.717), and best-corrected visual acuity ( t=7.033) at 6 months postoperatively ( P<0.05). A total of 237 differentially expressed proteins were identified between the RRDCD and RRD groups, with 63 upregulated and 174 downregulated. These proteins were involved in pathways such as extracellular matrix-receptor interaction, complement activation, coagulation, and lysosomal pathways. ELISA validation results showed that the expression trends of the three selected proteins in the RRDCD and RRD groups were consistent with the DIA proteomic analysis. Compared to the RRD group, proteins such as fibrin, coagulation factors, cathepsins, and trypsin inhibitors were significantly upregulated in the RRDCD group. Conclusions:The protein expression profile in vitreous fluid samples from RRDCD patients show significant alterations compared to the RRD group. These differential changes suggest that RRDCD is closely associated with complement and coagulation cascade activation, lysosomal pathways, and extracellular matrix remodeling.

Objective: To investigate the regulatory effect and mechanism of specific antagonist of acid-sensitive ion channel 3 (APETx2) on visceral sensitivity in mice with post-infectious irritable bowel syndrome (PI-IBS) ． Methods: The PI-IBS model was established by National Institutes of Health (NIH) mice infected with Trichinella spiralis．Gastrointestinal transport function was assessed by measuring the time to first black stool and the number of fecal pellets collected for 6 hours ; abdominal wall withdrawal reflex (AWR) was used to assess visceral sensitivity ; the expression of calcitonin gene-related peptide ( CGRP) in the colon tissue was detected by immunohistochemistry ; the expression of brain-derived neurotrophic factor (BDNF) and CGRP mRNA in the colon tissues was detected by quantitative real time polymerase chain reaction ( qRT-PCR) ． The expression levels of acid sensing ion channel 3 (ASIC3) ，CGRP，and transient receptor potential vanilloid 1 (TRPV1) protein in brain tissue were detected by Western blot analysis. Results: Compared with the control group，the PI-IBS group significantly reduced the time of first black stool，the number of fecal particles and AWR score within 6 hours significantly increased，the protein expression of CGRP in colon tissue，BDNF and CGRP mRNA significantly increased，and the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue significantly increased．Compared with the control group，the PI-IBS group significantly reduced the time to first black stool，the number of fecal particles and AWR score within 6 hours significantly increased，the expression of CGRP protein in colon tissue，the expression of BDNF and CGRP mRNA significantly increased，and the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue significantly increased ; compared with the PI-IBS group，the first time of black stool clearance in the APETx2 group was significantly prolonged，the number of fecal particles and AWR score within 6 hours were significantly reduced，the expression of CGRP protein in colon tissue，the expression of BDNF and CGRP mRNA was significantly reduced，the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue was significantly reduced，and the difference was statistically significant (P＜0. 05) ． Conclusion APETx2 can alleviate visceral sensitivity and regulate gastrointestinal motility in PI-IBS mice by downregulating the expression of BDNF，CGRP，ASIC3 and TRPV1．APETx2 may provide a new therapeutic option for the treatment of IBS.

Objective:To identify a novel bombesin bioactive peptide from the skin secretion of Hylarana Latouchii, and to explore its effect on insulin secretion in islet cells.Methods:The skin secretion from Hylarana Latouchii was extracted by electrical stimulation, and the single chain of bombesin peptide was cloned and sequenced. The peptide QUB2995 was synthesized via solid-phase synthesis, then purified using reversed-phase high performance liquid chromatography (HPLC). Matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF) was applied to validate. QPCR and ELISA were used to probe the effect of QUB2995 on insulin secretion in MIN6 and INS-1 cells.Results:A novel bombesin peptide named QUB2995 (GAFGDFLKGAAKA GALKILSIAQCKLSGTC) was found in the skin secretion of Hylarana Latouchii through molecular cloning. The bioactive peptide could significantly promote the proliferation and insulin secretion from mouse islet MIN6 cells and rat islet INS-1 cells. The effect reached a climax at the concentration of 10 -5 mol/L. Conclusion:A novel bombesin bioactive peptide named QUB2995 was found from Hylarana Latouchii. It could significantly promote insulin secretion in MIN6 cells of mouse islets and INS-1 cells of rat islets, indicating its potential in the treatment of diabetes.

Objective:To investigate the changes of ocular surface microbiota in obese patients before and after dietary intervention.Methods:From November 1, 2020 to May 1, 2021, 35 obese patients in the obesity management center of the Department of Endocrinology and Metabolic Diseases of Henan Provincial People′s Hospital were selected for a 4-week low-calorie dietary intervention of 1 600-1 800 kcal/day. The body weight, body mass index(BMI), body composition(body fat, body fat percentage, visceral fat grade, total body water, and skeletal muscle) were observed before and after dietary intervention. The characteristics of ocular surface flora in obese patients before and after intervention were analyzed by 16S rRNA sequencing.Results:The body weight, BMI, body fat, percentage of body fat, visceral fat grade and total body water decreased significantly after 4 weeks( P<0.05), while there was no significant difference in skeletal muscle( P>0.05). There was no significant difference of ocular surface flora α and β in diversity( P>0.05). Opportunistic pathogens Pseudomonas and Cutibacterium decreased significantly, while Faecalibacterium, Lachnospiraceae NK4A136 group, Oscillospiraceae UCG 002, and Blautia, which producing short chain fatty acids, increased significantly( P<0.05). Functional prediction analysis showed that the metabolic pathways such as degradation related pathways and insulin signaling pathways of volatile organic compounds(VOCs) were significantly enriched. Conclusion:After dietary intervention, opportunistic pathogenic bacteria decreased and short chain fatty acid producing bacteria increased in obese patients. The altered ocular surface flora may be related to the degradation of VOCs and the improvement of insulin sensitivity.